Avaliação da segurança farmacológica e eficácia de Plinia cauliflora (Mart.) Kausel em coelhos submetidos à um modelo de insuficiência cardíaca induzida por doxorrubicina

Abstract

Heart failure (HF) is a clinical disease characterized by impaired heart structure and / or function that promotes cardiac remodeling, such as distortions in the size, shape and function of the cardiac chambers. Among the main risk factors for the development of HF are systemic arterial hypertension and chemotherapy. In this away, In this sense, there is a stimulus for the use of medicinal plants in the treatment of heart disease. Plinia cauliflora (Mart.) Kausel is a possible alternative, because parts of the plant are used as a natural treatment for asthma, diarrhea and inflammation and studies show that phytochemicals such as proanthocyanidins and anthocyanins protect specifically against cardiovascular diseases. Thus, this paper proposes to evaluate the pharmacological safety and cardioprotective effects of P. cauliflora in a rabbit model of doxorubicin-induced heart failure. First of all, the pharmacological safety of P. cauliflora ethanolic extract (EEPC) was evaluated. For that, different groups of male New Zealand rabbits were treated orally with a single dose of ethanolic extract of P. cauliflora (EEPC) in the doses of 200 and 2000 mg/kg or vehicle (filtered water). After this treatment, acute behavioral changes and possible physiological changes were observed for 24 hours using the modified Irwin test, respiratory rate, heart rate, blood pressure, electrocardiogram and arterial blood gas analysis. In this pharmacological safety assessment, no significant behavioral or physiological changes were observed in any of the groups treated with EEPC. In addition, none of the EEPC doses affected respiratory rate or arterial blood gases, and there were no changes in mean arterial pressure or electrocardiographic parameters. Following these safety tests, the efficacy of EEPC against a DOX-induced HF model was evaluated. Thus, for HF induction, female rabbits of the New Zealand lineage received weekly administrations of 1.5 mg/kg of DOX intravenously for 6 weeks. Concomitantly, EEPC was administered orally at doses of 75 and 150 mg/kg daily for 42 days. Enalapril (5 mg/kg) was used as a reference cardioprotective medication and administered orally in daily doses for 42 days. At the end of the experimental period, blood pressure, heart rate, electrocardiographic profile, renal vascular reactivity, serum parameters including lipid profile, troponin, creatinine, nitrotirosine, malondialdehyde, nitrite and cerebral natriuretic peptide were evaluated. In addition, cardiac histopathological analyzes, ventricular morphometry and the antioxidant enzymatic system of the cardiac and renal tissues were investigated. The treatment with EEPC induced important responses where hemodynamic and functional changes were not observed and ventricular remodeling was prevented. In addition, treatment with EEPC reduced HF-induced renal dysfunction and satisfactorily modulated the tissue antioxidant defense system.